As a general rule, the organizers of clinical trials for the treatment of age-related diseases do all they can to focus on the least aged people possible. In this they are following the incentives placed upon them by regulators and investors, to try to avoid medical issues and deaths that occur for reasons unrelated to the treatment under assessment. One unlucky death or serious medical issue can sink an early stage trial, a program, or a company, regardless of cause, and very old people exhibit a high risk of such outcomes. So industry and academia ends up in the interesting position of not actually assessing potential age-slowing and rejuvenation therapies in the people who are most in need of such treatments. This seems a hard problem to fix, given the reasons why it exists.
Despite the growing numbers, older people remain systematically underrepresented in clinical trials (CTs) - creating what may be the most significant evidence gap in modern medicine. Systematic exclusion of older adults with multimorbidity, frailty, cognitive impairment, or those in long-term care settings creates a critical gap whereby clinicians must extrapolate treatment decisions from evidence derived predominantly from younger, healthier populations. This evidence gap cascades into inadequate clinical practice guidelines and suboptimal care standards, ultimately compromising care quality and patient safety for the very populations who most need evidence-based interventions.
Even when CTs do include older adults, they often employ restrictive eligibility criteria that exclude those with common geriatric conditions. The Systolic Blood Pressure Intervention Trial (SPRINT) exemplifies these limitations. Despite including participants aged ≥75 years with dedicated subgroup analyses, SPRINT excluded individuals with diabetes, prior stroke, heart failure, dementia, polypharmacy, and nursing home residence - conditions prevalent among older adults. This selective recruitment yielded a study population divergent from real-world older patients, potentially compromising external validity when extrapolating findings to broader older populations.
Link: https://doi.org/10.1016/j.jnha.2025.100597
View the full article at FightAging
